PUBLICATION
Trehalose Treatment in Zebrafish Model of Lafora Disease
- Authors
- Della Vecchia, S., Ogi, A., Licitra, R., Abramo, F., Nardi, G., Mero, S., Landi, S., Battini, R., Sicca, F., Ratto, G.M., Santorelli, F.M., Marchese, M.
- ID
- ZDB-PUB-220625-18
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(12): (Journal)
- Registered Authors
- Keywords
- Lafora disease, autophagy, neuroinflammation, progressive myoclonic epilepsies, trehalose
- MeSH Terms
-
- Animals
- Lafora Disease*/drug therapy
- Lafora Disease*/genetics
- Lafora Disease*/metabolism
- Mutation
- Protein Tyrosine Phosphatases, Non-Receptor/genetics
- Protein Tyrosine Phosphatases, Non-Receptor/metabolism
- Seizures
- Trehalose/pharmacology
- Ubiquitin-Protein Ligases/genetics
- Zebrafish/metabolism
- PubMed
- 35743315 Full text @ Int. J. Mol. Sci.
Citation
Della Vecchia, S., Ogi, A., Licitra, R., Abramo, F., Nardi, G., Mero, S., Landi, S., Battini, R., Sicca, F., Ratto, G.M., Santorelli, F.M., Marchese, M. (2022) Trehalose Treatment in Zebrafish Model of Lafora Disease. International Journal of Molecular Sciences. 23(12).
Abstract
Mutations in the EPM2A gene encoding laforin cause Lafora disease (LD), a progressive myoclonic epilepsy characterized by drug-resistant seizures and progressive neurological impairment. To date, rodents are the only available models for studying LD; however, their use for drug screening is limited by regulatory restrictions and high breeding costs. To investigate the role of laforin loss of function in early neurodevelopment, and to screen for possible new compounds for treating the disorder, we developed a zebrafish model of LD. Our results showed the epm2a-/- zebrafish to be a faithful model of LD, exhibiting the main disease features, namely motor impairment and neuronal hyperexcitability with spontaneous seizures. The model also showed increased inflammatory response and apoptotic death, as well as an altered autophagy pathway that occurs early in development and likely contributes to the disease progression. Early administration of trehalose was found to be effective for rescuing motor impairment and neuronal hyperexcitability associated with seizures. Our study adds a new tool for investigating LD and might help to identify new treatment opportunities.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping